The overall goal of this project is to provide surgeons with a tool in the operating room to correctly identify the margins of a tumor during resection. One of the most important goals for a surgeon after tumor resection is to achieve negative tumor margins. Failure to completely remove the entire tumor is one of the leading risk factors for recurrence and can lead to significant problems for the patient including eventual metastasis. Here we are proposing to develop a novel tool to help guide surgeons in real-time to identify tumor margins. The proposed product consists of two components 1) A handheld Raman device, which will be fabricated in-house at Stanford University and 2) Raman-active gold nanoparticles, which are commercially available. Our strategy involves modifying the surface of these gold nanoparticles with tumor targeting agents. After administration to the tumor area, the nanoparticles would ideally localize and bind specifically to the tumor itself, becoming a contrast agent for our handheld Raman scope to sensitively detect. A radiometric imaging strategy can then be used to quantify specific vs. nonspecific contrast agent binding, resulting in improved tumor-to-background ratios. This novel tool is intended to aid surgeons by identifying tumor margins sensitively and specifically in real time during tumor resection and as a verification tool after tumor excision. Raman spectroscopy is an optical technique that offers unsurpassed sensitivity (on the order of pM) and multiplexing capabilities to the field of molecular imaging, and incorporating it into the operating room has the potential to significantly improve the surgeon's ability to obtain negative resection margins. The approach is expected to be low risk for clinical translation because Raman endoscopes have previously been used in humans, and because gold based nanoparticles are relatively inert and some constructs have already been approved by the FDA for human use. The results obtained from this proposal could significantly accelerate the translation of this novel strategy into the clinic. In addition, harnessing the ultrasensitive detection and multiplexing capabilities of Raman spectroscopy for identifying tumor margins could significantly decrease the chances of recurrence and repeat visits to the operating room thus impacting the survival rate of cancer patients.